Diagnosis of Noonan syndrome and related disorders using target next generation sequencing
Conclusion:
Here we show how molecular testing of RASopathies by targeted NGS could allow an early and accurate diagnosis for all enrolled patients, enabling a prompt diagnosis especially for those patients with mild, non-specific or atypical features, in whom the detection of the causative mutation usually requires prolonged diagnostic timings when using standard routine. This approach strongly improved genetic counselling and clinical management. (Source: BMC Medical Genetics - Latest articles)
Source: BMC Medical Genetics - Latest articles - January 23, 2014 Category: Genetics & Stem Cells Authors: Francesca LepriRossana ScavelliMaria DigilioMaria GnazzoSimona GrottaMaria DenticiElisa PisaneschiPietro SirletoRossella CapolinoAnwar BabanSerena RussoTiziana FranchinAdriano AngioniBruno Dallapiccola Source Type: research
Autism traits in the RASopathies
Conclusions
Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs. (Source: Journal of Medical Genetics)
Source: Journal of Medical Genetics - December 18, 2013 Category: Genetics & Stem Cells Authors: Adviento, B., Corbin, I. L., Widjaja, F., Desachy, G., Enrique, N., Rosser, T., Risi, S., Marco, E. J., Hendren, R. L., Bearden, C. E., Rauen, K. A., Weiss, L. A. Tags: Editor's choice, Connective tissue disease Cognitive and behavioural genetics Source Type: research
Selfish spermatogonial selection of HRAS mutations [Genetics]
The RAS proto-oncogene Harvey rat sarcoma viral oncogene homolog (HRAS) encodes a small GTPase that transduces signals from cell surface receptors to intracellular effectors to control cellular behavior. Although somatic HRAS mutations have been described in many cancers, germline mutations cause Costello syndrome (CS), a congenital disorder associated with predisposition... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - December 10, 2013 Category: Science Authors: Giannoulatou, E., McVean, G., Taylor, I. B., McGowan, S. J., Maher, G. J., Iqbal, Z., Pfeifer, S. P., Turner, I., Burkitt Wright, E. M. M., Shorto, J., Itani, A., Turner, K., Gregory, L., Buck, D., Rajpert-De Meyts, E., Looijenga, L. H. J., Kerr, B., Wilk Tags: Biological Sciences Source Type: research
Cutaneous Manifestations in Costello and Cardiofaciocutaneous Syndrome: Report of 18 Cases and Literature Review
The objective of this prospective observational study was to describe the spectrum of skin findings in CS and CFCS and to highlight those specific to each of these two diseases. Patients with a confirmed diagnosis of CFCS or CS underwent a systematic skin examination during the annual workshop organized by the French CS association in 2007 and 2009 in Bordeaux, France. Eighteen patients were included in the study. Specific skin abnormalities, including cutis laxa, curly hair, pruritus, and hyperhidrosis, are shared by CFCS and CS, whereas others may help to differentiate between these two syndromes. Acanthosis nigricans, p...
Source: Pediatric Dermatology - November 13, 2013 Category: Dermatology Authors: Fanny Morice‐Picard, Khaled Ezzedine, Marie‐Ange Delrue, Benoit Arveiler, Patricia Fergelot, Alain Taïeb, Didier Lacombe, Franck Boralevi Tags: Reviews Source Type: research
HRAS mutations in bladder cancer at an early age and the possible association with the Costello Syndrome
& Ellen C Zwarthoff (Source: European Journal of Human Genetics)
Source: European Journal of Human Genetics - October 30, 2013 Category: Genetics & Stem Cells Authors: Willemien BeukersAleksander HercegovacEllen C Zwarthoff Tags: Urinary Bladder Neoplasms genes Ras mosaicism Costello Syndrome Source Type: research
Two new cases with costello syndrome.
Abstract
Costello syndrome (CS) was described in 1977 by Costello who reported two unrelated children with a new syndrome comprising short stature, redundant skin of the neck, palms, soles, and fingers, curly hair, papillomata around the mouth and nares, and mental retardation. Several additional cases have been reported since then. Herein we report two patients with Costello syndrome; one of these patients had associated mesenteric cyst.
PMID: 24021445 [PubMed - in process] (Source: Dermatol Online J)
Source: Dermatol Online J - September 16, 2013 Category: Dermatology Authors: Aytekin S, Alyamac G Tags: Dermatol Online J Source Type: research
The RASopathies.
Abstract
The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. These disorders include neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. Because of the common underlying Ras/MAPK pathway dysregulation, the RASopathies exhibit numerous overlapping phenotypic features. The Ras/MAPK pathway...
Source: Annual Review of Genomics and Human Genetics - July 15, 2013 Category: Genetics & Stem Cells Authors: Rauen KA Tags: Annu Rev Genomics Hum Genet Source Type: research
Medulloblastoma in a patient with the PTPN11 p.Thr468Met mutation
We present a patient with NSML caused by the recurrent PTPN11 mutation c.1403C > T (p.Thr468Met) in whom medulloblastoma was diagnosed at age 10 years. Medulloblastoma could therefore be part of the tumor spectrum associated with this disorder. © 2013 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - June 27, 2013 Category: Genetics & Stem Cells Authors: Julia Rankin, John Short, Peter Turnpenny, Bruce Castle, C. Oliver Hanemann Tags: Clinical Report Source Type: research
Orthopedic manifestations and implications for individuals with Costello syndrome
This study further defines the orthopedic manifestations affecting individuals with Costello syndrome. We studied 43 participants and performed medical records review, clinical examinations and orthopedic inquiry forms. In 23 participants, hip and or spinal imaging assessments were completed. Serial radiographs were analyzed when available. A total of 25 orthopedic manifestations were identified. Ten manifestations were seen in the majority of the participants: hypotonia (87%), ligamentous laxity (85%), scoliosis (63%), kyphosis (58%), characteristic hand deformities (85%), ulnar deviation of the wrist (63%), elbow (55%) a...
Source: American Journal of Medical Genetics Part A - June 27, 2013 Category: Genetics & Stem Cells Authors: Stacey Detweiler, Mihir M. Thacker, Elizabeth Hopkins, Laura Conway, Karen W. Gripp Tags: Research Article Source Type: research
Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi‐detector row computed tomography
In this study, images reconstructed by multi‐detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hy...
Source: Congenital Anomalies - June 10, 2013 Category: Genetics & Stem Cells Authors: Masashi Takahashi, Hirofumi Ohashi Tags: Original Article Source Type: research
Keratoconus in Costello syndrome
Abstract
Keratoconus is a corneal dystrophy with progressive corneal thinning resulting in abnormal corneal shape and astigmatism. Corneal hydrops and rupture can occur and corneal transplant may become necessary. While keratoconus is rare in the general population occurring in about 1/2,000 individuals, it is more common in individuals with intellectual disability and syndromic conditions. Connective tissue abnormalities, most typically brittle cornea syndrome, have frequently been reported in association with keratoconus. Here, we report on bilateral keratoconus with acute hydrops in the left eye of a 24‐year‐old mal...
Source: American Journal of Medical Genetics Part A - March 13, 2013 Category: Genetics & Stem Cells Authors: Karen W. Gripp, Laurie A. Demmer Tags: Clinical Report Source Type: research
‘Cobblestone’ papillomatous linear papules of the upper lip: a new sign of Costello syndrome
(Source: British Journal of Dermatology)
Source: British Journal of Dermatology - January 18, 2013 Category: Dermatology Authors: C. Pernet, C. Baumann, H. Cavé, B. Guillot, D. Bessis Tags: Correspondence Source Type: research
Delayed primary diagnosis of LEOPARD syndrome type 1
To the Editor: LEOPARD syndrome (LS) is a rare autosomal dominant genodermatosis. It is characterized by multiple Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary valve stenosis, Abnormal genitals, Retarded growth, and Deafness. Like neurofibromatosis type 1, Noonan syndrome, Costello syndrome, and cardiofaciocutaneous syndrome, it belongs to the group of neurocardiofaciocutaneous diseases. Zeisler and Becker reported the first case of LS in 1936, and later the acronym of the syndrome was coined because of the multiple lentigines that resemble the fur pattern of a leopard. The acronym has bee...
Source: Journal of the American Academy of Dermatology - January 14, 2013 Category: Dermatology Authors: Janina Staub, Anne Behnecke, Martin Leverkus Tags: JAAD Online Source Type: research
Ras/MAPK syndromes and childhood hemato-oncological diseases.
Abstract
Noonan syndrome (NS) is an autosomal-dominant disease characterized by distinctive facial features, webbed neck, cardiac anomalies, short stature and cryptorchidism. NS exhibits phenotypic overlap with Costello syndrome and cardio-facio-cutaneous (CFC) syndrome. Germline mutations of genes encoding proteins in the RAS/mitogen-activated protein kinase (MAPK) pathway cause NS and related disorders. Germline mutations in PTPN11, KRAS, SOS1, RAF1, and NRAS have been identified in 60-80 % of NS patients. Germline mutations in HRAS have been identified in patients with Costello syndrome and mutations i...
Source: International Journal of Hematology - December 19, 2012 Category: Hematology Authors: Aoki Y, Matsubara Y Tags: Int J Hematol Source Type: research
